Buprenorphine is a known treatment for narcotic addiction and may be used to treat other conditions, such as psychiatric disorders, depression, and schizophrenia. Generally, buprenorphine is administered with a sublingual tablet (commercially available as Suboxone) to treat addiction. However, long term maintenance treatment through this route is problematic as it creates withdrawal symptoms due to the steep rise and drop of the drug concentrations in plasma after each dose. Patient compliance and the potential for abuse are also drawbacks for this method of treatment.
Other known delivery methods of buprenorphine include a transdermal patch, sesame oil based formulations, biodegradable and non-biodegradable implants—which can be painful to administer as they require local anesthesia at the implant site. A sustained release injectable microsphere formulation would maintain a steady plasma concentration, preventing withdrawal symptoms.
Injectable polymer solutions containing buprenorphine have been developed to provide sustained release buprenorphine. Upon injection, the solvent diffuses away from the injection site, leaving the buprenorphine containing polymer matrix to release the drug at a controlled rate. However, the solvents utilized, such as N-methyl pyrolidone, in this system are toxic in view of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the U.S. Pharmacopeial Convention.
While several methods have been used to achieve a sustained release injectable formulation, the microspheres either had a drug load that was too low to be commercially viable—less than about 2%—were produced with an additional polymer coating, creating manufacturing difficulties, included toxic solvents, or did not provide the desired length of sustained release. It would be desirable to produce a commercially acceptable injectable sustained release microsphere formulation that has both a high drug load and a low initial burst release.